1. Field of the Invention
The invention relates to water-soluble, chlorhexidine-containing compositions and to the use thereof. The compositions contain chlorhexidine in the form of the free base or in the form of a chlorhexidine disalt.
2. Discussion of the Background
Clorhexidine (CHD), chemically identified as 1,1′-hexamethylenebis[5-(p-chlorophenyl)biguanide], is a substance having a strongly basic action with only very low water solubility. By reacting the chlorhexidine base with acids, a large number of salts that are also sparingly water-soluble can be obtained. However, some salts of chlorhexidine with sugar acids are water-soluble. Chlorhexidine base, and especially the water-soluble chlorhexidine digluconate, a salt of D(+)-gluconic acid with chlorhexidine, represent important antibacterial substances for use in both the human and the animal sector. Their low toxicity and compatibility with cationic and non-ionic detergents should be highlighted. Chlorhexidine digluconate (CHD-gluc) is commercially available as a 20 wt. % aqueous solution. Liquid formulations containing chlorhexidine are modified in many different ways and used as an antibacterial additive in cosmetics, for skin disinfection, treatment of wounds, in veterinary medicine as an udder disinfectant, and also for disinfecting surfaces.
CHD gluconate solutions are subject to the requirements of the European Pharmacopoeia or the United States Pharmacopeia with respect to their composition and appearance. One of the purity requirements is the content of p-chloroaniline, which is limited to 500 ppm. In an inversion of the formation of CHD (═CHD base) from hexamethylene-biscyanoguanidine and p-chloroaniline according to the following equation: p-chloroaniline can be reversibly split off during the salt formation of the CHD base with D(+)-gluconic acid δ-lactone, the internal ester of D(+)-gluconic acid, in the aqueous phase, and on standing, i.e. storage of these solutions. As the storage period increases, the solutions take on a yellow to brownish discoloration. This decomposition of chlorhexidine digluconate solutions is dependent on the pH of the solution and particularly on the storage temperature. Investigations have shown that, when a 20 wt. % solution of chlorhexidine digluconate is stored at 40° C., the permitted p-chloroaniline values are exceeded after about one month. Even frequently used solutions containing CHD digluconate and other microbicidally active substances are subject to this hydrolysis to varying degrees.
One frequently used combination contains chlorhexidine digluconate and N-cetyl-N,N,N-trimethylammonium bromide (cetrimide) as active substances in dilute aqueous or alcoholic solutions. Even these solutions have inadequate storage stability. Solid compositions containing chlorhexidine or a salt thereof and cetrimide or similar microbicides, which dissolve in water to form a clear solution and are inherently stable even at an elevated storage temperature, have been unknown up to the present.
The object of the present invention is therefore to provide such biocidal mixtures, from which ready-to-use solutions can be obtained by adding water.